An important ability of the visual system is that it is able to detect motion in the world around us. The detection of motion is first found in the retina, and this ability arises from the presence of cells that are uniquely sensitive to the direction of a moving object. These cells are known as ON-OFF direction selective ganglion cells, because they respond to both the on and off-set of light, as well as to objects moving in a preferred direction. How these cells develop these particular response properties is unknown, although it is known that these cells are present at eye opening in mouse, and behave much like they would in an adult mouse retina. Mice are born with their eyes closed, and they remain so for the first two weeks of life. During this period of time vision cannot occur and the retina is still unresponsive to light, being in a state a rapid development. However, for these two weeks the retina is not merely silent, but rather displays a large degree of spontaneous neural activity, a phenomenon known as retinal waves. Retinal waves are known to be important in shaping the visual circuits that will function once the eyes open and vision is initiated. This project seeks to identify whether spontaneous activity in the immature retina that occurs before eye opening influences the development of ON-OFF direction selective ganglion cells. To accomplish this I will silence retinal activity by developing multiple genetic techniques to silence activity. I will then use state of the art multielectrode arrays to record the response of many neurons to the presentation of directional stimuli and test if these properties have been abolished or altered when spontaneous activity is inhibited. This proposal will help to clarify a long standing question in visual neuroscience regarding the detection of moving objects as well as help us to better understand the role of spontaneous activity in the developing nervous system. PUBLIC HEALTH RELEVANCE: The proposed research will provide us with broader insight into the role of spontaneous activity in the developing nervous system. To date, numerous neural structures, including the retina, hippocampus, spinal cord and cortex have been shown to demonstrate robust patterns of spontaneous activity during periods of early development, independent of sensory input. These patterns of spontaneous activity influence the ultimate development of functional circuitry in the CNS, and a full understanding of their effects on the development of neural circuits will have a far reaching impact on our ability to diagnose and treat neonatal nervous system diseases.